The DOI matches its Crossref record; 39 of the 39 references it cites were found in a registry or an index.
Metformin inhibits melanoma development through autophagy and apoptosis mechanisms
Open accessAbstract
Metformin is the most widely used antidiabetic drug because of its proven efficacy and limited secondary effects. Interestingly, recent studies have reported that metformin can block the growth of different tumor types. Here, we show that metformin exerts antiproliferative effects on melanoma cells, whereas normal human melanocytes are resistant to these metformin-induced effects. To better understand the basis of this antiproliferative effect of metformin in melanoma, we characterized the sequence of events underlying metformin action. We showed that 24 h metformin treatment induced a cell cycle arrest in G0/G1 phases, while after 72 h, melanoma cells underwent autophagy as demonstrated by electron microscopy, immunochemistry, and by quantification of the autolysosome-associated LC3 and Beclin1 proteins. In addition, 96 h post metformin treatment we observed robust apoptosis of melanoma cells. Interestingly, inhibition of autophagy by knocking down LC3 or ATG5 decreased the extent of apoptosis, and suppressed the antiproliferative effect of metformin on melanoma cells, suggesting that apoptosis is a consequence of autophagy. The relevance of these observations were confirmed in vivo, as we showed that metformin treatment impaired the melanoma tumor growth in mice, and induced autophagy and apoptosis markers. Taken together, our data suggest that metformin has an important impact on melanoma growth, and may therefore be beneficial in patients with melanoma.
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Cites
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Self-citation
Cited by
MTOR: a pharmacologic target for autophagy regulation
Kim, Y. C., & Guan, K.-L. (2015) · Journal of Clinical Investigation · doi:10.1172/jci73939 · Cited by 2,126
Autophagy—a key player in cellular and body metabolism
Kim, K. H., & Lee, M.-S. (2014) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2014.35 · Cited by 963
Senescence and aging: the critical roles of p53
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Cancer metabolism: current perspectives and future directions
Muñoz-Pinedo, C., El Mjiyad, N., & Ricci, J.-E. (2012) · Cell Death & Disease · doi:10.1038/cddis.2011.123 · Cited by 385
Metadata
- Authors
- Tomic, T., Botton, T., Cerezo, M., Robert, G., Luciano, F., Puissant, A., Gounon, P., Allegra, M., Bertolotto, C., Bereder, J.-M., Tartare-Deckert, S., Bahadoran, P., Auberger, P., Ballotti, R., & Rocchi, S.
- Venue
- Cell Death & Disease
- Published
- 2011-09-01
- Volume
- 2
- Issue
- 9
- Pages
- e199-e199
- ISSN
- 2041-4889 (ISSN-L)
- OpenAlex
- W1987334928
- Cited by
- 301
- References
- 39
- FWCI
- 8.23
- Type
- journal article
- Language
- en
- Open access
- gold
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- Tomic, T., Botton, T., Cerezo, M., Robert, G., Luciano, F., Puissant, A., Gounon, P., Allegra, M., Bertolotto, C., Bereder, J.-M., Tartare-Deckert, S., Bahadoran, P., Auberger, P., Ballotti, R., & Rocchi, S. (2011). Metformin inhibits melanoma development through autophagy and apoptosis mechanisms. Cell Death & Disease. https://doi.org/10.1038/cddis.2011.86
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